Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Disease Progression

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Quality of Life

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Channel Blockers

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Piperidine

Enzyme Inhibitors

Patients will receive 200/300 mg of niraparib daily for study period of up to 24 weeks. Patients will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Niraparib will be supplied in oral formulation as 100 mg capsules. The starting dose of Niraparib will be based upon the patient's baseline body weight and/or platelet count:

Participants with a baseline body weight ≥77 kg and baseline platelet count ≥150 x 109/L will be administered niraparib 300 mg daily.

Participants with a baseline body weight \<77 kg or baseline platelet count \<150 x 109/L will be administered niraparib 200 mg daily.

The dose of Niraparib can be reduced in 100 mg increments, to a minimum of 100 mg, per protocol. Dose escalations are not permitted.

Patients in this arm will be managed symptomatically and will be treated as per the standard of care at each participating site. ASC could involve regular specialist follow up; structured assessment of physical, psychological, and social problems; and appropriate treatment, including palliative radiotherapy and steroids.

Niraparib (\[3S\]-3-\[4-\[7-(aminocarbonyl)-2H-indazol-2-yl\] phenyl\] piperidine \[tosylate monohydrate salt\]) is an orally available, potent, and highly selective PARP1 and PARP2 inhibitor. The excipients for niraparib are lactose monohydrate and magnesium stearate. Niraparib will be supplied in bottles containing 72 capsules of 100 mg. The capsules should be swallowed whole with water. The capsules should not be chewed or crushed and can be taken without regard to meals.

Niraparib Oral Product

ASC could involve regular specialist follow up; structured assessment of physical, psychological, and social problems; and appropriate treatment, including palliative radiotherapy and steroids.

Active Symptom Control

Dean Fennell

Multicentre, 2 arm, open-label UK randomised phase II trial to determine the efficacy of niraparib versus active symptom control (ASC) in patients who have relapsed after previously receiving platinum based systemic therapy. 84 patients will be recruited from approximately 10 UK trial network sites.

Mesothelioma is a cancer that is caused by exposure to asbestos, an environmental contaminant. This cancer is incurable and lacks effective treatment, particularly after initial chemotherapy. There has not been a licenced therapy for mesothelioma since 2003, and no treatment has yet demonstrated an improvement in survival following initial chemotherapy. There is an urgent need to explore more effective approaches to therapy. Targeted treatments offer potential hope for the treatment of mesothelioma. A class of drugs called PARP (Poly Adenosine Diphosphate-ribose polymerase) inhibitors have already been proven to improve the survival of patients with breast and ovarian cancers, that carry specific mutations. Mesothelioma has been shown in a recent trial to respond to this class of agent. Further investigation is warranted to test whether PARP inhibitors could be a new treatment option for patients. As with ovarian cancer studies of the past, the NERO trial will test a PARP inhibitor (niraparib) after successful treatment with chemotherapy. Patients whose tumours shrink or stabilise following chemotherapy are expected to have a greater chance of benefit from niraparib. It's not known if niraparib will be able to improve survival of patients with mesothelioma, or indeed whether or not toxicity could occur without benefit. For that reason, patients will be randomised with a 2:1 chance of receiving the drug. Those patients who do not receive niraparib will be closely monitored for signs of early tumour growth so that they can go on to receive an alternative treatment if necessary. If the NERO trial is positive, this study will lead to the approval of a new medicine for use around the world, one that would extend the life expectancy of patients for the first time following initial chemotherapy. NERO will recruit 84 patients over 12 months. Those randomised to receive niraparib will receive a daily dose of 200 mg or 300mg for up to 24 weeks within the trial.

NERO is a multicentre, 2 arm, open-label UK randomised phase II trial comparing Niraparib versus ASC in patients with previously treated mesothelioma.

Niraparib Efficacy in Patient With Unresectable Mesothelioma

Niraparib Efficacy in Patient With Unresectable Mesothelioma: A Randomised Phase II Trial of Niraparib Versus Active Symptom Control in Patients With Previously Treated Mesothelioma

IPD will be made available, including data dictionaries, for approved data sharing requests. Individual participant data will be shared that underlie the results after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available. Pseudonymised participant data within the clinical trial dataset will be available for sharing via controlled access by authorised Southampton Clinical Trials Unit (SCTU) staff. The request for data access will need to detail the specific requirements and the proposed research, statistical analysis, publication plan and evidence of research group qualifications. Data will be shared once all parties have signed relevant data sharing documentation covering SCTU conditions for sharing and if required, an additional data sharing agreement from the sponsor. Proposals should be directed to ctu@soton.ac.uk.

Response, progression-free and overall survival will be correlated with somatic alteration of HR genes

Progression-free survival is the determined by modified RECIST (pleural disease), RECIST 1.1 (for non-pleural disease), investigator reported progression or death from any cause (whichever event comes first)

Time from randomisation to death from any cause

The best overall response is the best response recorded from the start of treatment until disease progression or death

Stable disease, partial or complete response

Time from complete or partial response (where this occurs) until progression or death

Assessed by summarising the percentage of the received dose relative to the intended dose at each cycle

Summary statistics and listings will be reported for patients in the safety population and will be summarised by treatment arm with classification by the latest version of MedDRA. Grade will be reported on the CTCAE toxicity scale (version 5.0). Both all cause and treatment related or emergent AEs will be included in the analysis.

University of Southampton

British Lung Foundation

University Hospital Southampton NHS Foundation Trust

Vinorelbine

Vinca Alkaloids

Tubulin Modulators

Antimitotic Agents

Active symptom control includes palliative care and standard care methods used to manage symptoms

Active symptom control (ASC) as per local practice plus vinorelbine administered at a dose of 60mg/m2 orally on day 1, day 8 and day 15 on a 3- weekly cycle, incrementing to 80mg/m2 weekly on a 3-weekly cycle in the absence of any significant toxicity for subsequent cycles. Patients will continue chemotherapy until evidence of radiological progression (or unacceptable toxicity or patient withdrawal).

Vinorelbine was first licensed in the UK for Non-Small Cell Lung Cancer (NSCLC) and advanced breast cancer in 1997. Vinorelbine (Navelbine®) is a semi-synthetic, third generation, vinca alkaloid. The cytotoxic effect of vinorelbine is through the disruption of mitotic spindle formation, blocking mitosis at the G2-M stage resulting in cell death.

Dean Fennell, Professor

This study is for patients with malignant mesothelioma of the lung lining (called pleura) who have had previous chemotherapy with a platinum-based regimen whose disease has progressed. Malignant pleural mesothelioma (MPM) is an aggressive, frequently drug resistant, and incurable disease that is increasing in incidence in the UK and worldwide. All patients with MPM will relapse following first line chemotherapy and at present, there is no standard treatment available for patients in the second line setting. The vinca alkaloid chemotherapy drug vinorelbine has shown promising activity in a single arm UK trial. However to date, there has been no randomised evaluation of vinorelbine in mesothelioma in the second line setting. In addition, there have been no trials which have looked at underlying molecular changes in mesothelioma which may predict vinorelbine efficacy; This might allow vinorelbine to be used in patients only where there is a chance of benefit. Studies suggest that vinorelbine requires a gene called BRCA1 (shown to be absent in 38% of mesothelioma cases) in order to induce cell death in mesothelioma. The VIM trial aims to establish whether vinorelbine in patients with MPM helps them live longer and whether the BRCA1 gene is helpful in selecting patients most likely to benefit from treatment.

Patients will be randomised (1:2) to receive either active symptom control (ASC) (which is all supportive care deemed necessary for pain management excluding disease modifying treatment) or ASC with vinorelbine. Patients will continue vinorelbine treatment until evidence of disease progression (or unacceptable toxicity to the drug or patient withdrawal). If vinorelbine activity is demonstrated, we will use the results from this trial to inform the design of a future phase III trial.

Vinorelbine in Mesothelioma

A Randomised Phase II Trial of Oral Vinorelbine as Second Line Therapy for Patients With Malignant Pleural Mesothelioma

Anti-tumour activity of vinorelbine will be measured by overall survival, time from randomisation to death.

Anti-tumour activity of vinorelbine will also be measured by progression free survival. We will document time from randomisation to any disease progression and/or death, defined according to strict RECIST v1.1. Lesions will be compared with baseline measurements to assess progression

The toxicity profile of oral vinorelbine in this setting will be used to assess safety. An independent data monitoring committee will convene and assess safety 6 months after the first patient has been randomised. If the trial is deemed safe to continue then safety will be assessed again approx every 6 months. Toxicity data will be assessed alongside serious adverse events.

Tumour and blood samples will be collected for future translational research. BRCA1 expression as a putative predictor of vinorelbine sensitivity will be measured primarily in the samples.

Pierre Fabre Laboratories

Wales Cancer Trials Unit

Digestive System Diseases

Cholangiocarcinoma

Biliary Tract Neoplasms

Gallbladder Neoplasms

Adenocarcinoma

Carcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Diseases

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Micronutrients

Anti-Infective Agents

Hematinics

Antiemetics

Gastrointestinal Agents

Emetics

Vitamins

Gemcitabine

Oxaliplatin

Leucovorin

Fluorouracil

Anti-Bacterial Agents

Levoleucovorin

Cisplatin

Antibiotics, Antitubercular

Folic Acid

Vitamin B Complex

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid \& 5FU)

Active Symptom Control: monthly clinical review and active symptom control as needed, including biliary drainage, antibiotics, analgesia, steroids, anti-emetics, other palliative treatment for symptom control, palliative radiotherapy, blood transfusion.

L-folinic acid 175mg (or folinic acid 350mg) q14d, up to 12 cycles

L-folinic acid

5 FU 400 mg/m2 (bolus), 2400 mg/m2 (infusion), q 14d, up to 12 cycles

5 FU

Oxaliplatin 85mg/m2, q 14d, up to 12 cycles

Juan Valle, Prof

The purpose of this study is to determine whether fit patients (with ECOG performance score of 0-1) with advanced biliary tract cancer (ABC) benefit from chemotherapy in the second-line setting (after prior therapy with cisplatin and gemcitabine) in terms of overall survival.

Active chemotherapy drugs for the treatment of ABC include gemcitabine, fluoropyrimidines and platinum agents. The randomized NCRN phase III ABC-02 trial provided level A evidence supporting first-line combination cisplatin and gemcitabine (CisGem) chemotherapy in ABC. To date, there is no randomized data to support the use of second-line chemotherapy in ABC. In this setting only a small number of retrospective and prospective (phase II) studies employing multiple different chemotherapy schedules have been conducted (level C). Thus, active symptom control (ASC) is the current standard of care after development of resistance to first-line chemotherapy. Oxaliplatin has activity in several gastrointestinal tumours and has synergistic activity with a favourable toxicity profile when used in combination with 5-FU. Several studies using mFOLFOX for biliary tract tumours have provided promising efficacy data and acceptable toxicity.

The aim of this trial is to determine if patients with ABC benefit with respect to survival from the addition of mFOLFOX chemotherapy to ASC in the second-line setting after progression to first-line treatment with CisGem. This study will establish the standard of care for patients with ABC who have progressed on first line CisGem chemotherapy.

This is a randomised phase III, multi-centre, controlled, open-label trial of patients with advanced biliary tract cancer with evidence of disease progression after prior CisGem chemotherapy treatment. Eligible patients (ECOG 0-1, adequate haematological, renal and liver function, adequate biliary drainage, with no evidence of ongoing infection) will be randomized to receive either ASC ("standard" arm) or ASC with oxaliplatin/5-FU chemotherapy ("experimental" arm). The total number of participants planned is 162 (randomized 1:1). At randomisation the following factors will be controlled for: serum albumin level, platinum sensitivity (determined from first-line therapy) and locally advanced vs metastatic disease.

The primary end point is overall survival. Quality of life and economic evaluation will assess the impact on patients and relative cost effectiveness of the intervention. Archival paraffin-embedded tissue will be collected at baseline and prospective blood samples (whole blood, serum and plasma) will be collected for translational research.

Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers

A Phase III, Randomised, Multicentre Open-label Study of Active Symptom Control (ASC) Alone or ASC With Oxaliplatin/ 5F-U Chemotherapy for Patients With Locally Advanced/ Metastatic Biliary Tract Cancers Previously Treated With Cisplatin/ Gemcitabine Chemotherapy.

Clinical progression assessed monthly, radiological progression assessed to RECIST criteria every 12 weeks for patients in the chemotherapy arm.

Events will be classified according to CTCAE V4.03

Assessed from patient completed questionnaire data: QLQ-C30 and QoL BiL

Estimated from Euroqol and survival using published utility tariffs

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
Vinorelbine in Mesothelioma	NCT02139904	Mesothelioma	Vinorelbine Active Symptom ...	18 Years -	Wales Cancer Trials Unit
Vinorelbine in Mesothelioma	NCT02139904	Mesothelioma	Vinorelbine Active Symptom ...	18 Years -	Wales Cancer Trials Unit
Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers	NCT01926236	Biliary Tract C... Gallbladder Can... Cholangiocarcin... Ampullary Cance...	Active Symptom ... L-folinic acid 5 FU Oxaliplatin	18 Years -	The Christie NHS Foundation Trust
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
Vinorelbine in Mesothelioma	NCT02139904	Mesothelioma	Vinorelbine Active Symptom ...	18 Years -	Wales Cancer Trials Unit
Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers	NCT01926236	Biliary Tract C... Gallbladder Can... Cholangiocarcin... Ampullary Cance...	Active Symptom ... L-folinic acid 5 FU Oxaliplatin	18 Years -	The Christie NHS Foundation Trust

Spots Global Cancer Trial Database for active symptom control